scholarly journals CSIG-13. TRPM7 INDUCES TUMORIGENESIS AND STEMNESS THROUGH NOTCH ACTIVATION IN GLIOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii30-ii30
Author(s):  
Jingwei Wan ◽  
Alyssa Guo ◽  
Mingli Liu
Keyword(s):  
Notch Signaling ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
Notch Signaling Pathway ◽  
Normal Brain ◽  
Diffuse Astrocytoma ◽  
Notch1 Signaling ◽  
Signaling Activation ◽  
Proliferation And Invasion

Abstract Our group found that the inhibitory effect of TRPM7 on proliferation and invasion of human glioma cell is mediated by multiple mechanisms. TRPM7 regulates miR-28-5p expression, which suppresses cell proliferation and invasion in glioma cells by targeting Ras-related protein Rap1b. In particular, our group found that TRPM7 channels regulate glioma stem cell (GSC) growth/proliferation through STAT3 and Notch signaling. However, which Notch component(s) is crucial for its activity regulated by TRPM7, and its relationship with other GSC markers, such as CD133 and ALDH1, remain unclear. In the current project, we elucidate the mechanisms of TRMP7’s regulation of Notch signaling pathway that contribute to the development and progression of glioma and maintenance of self-renewal and tumorigenicity of GSC using multiple glioma cell lines (GC) with different molecular subtypes and GSCs derived from the GC lines. 1) We first analyzed TRPM7 expression using the Oncomine database (https://www.oncomine.org) and found that the TRPM7 mRNA expression is significantly increased in anaplastic astrocytoma, diffuse astrocytoma, and GBM patients compared to that in normal brain tissue controls. 2) TRPM7 is expressed in GBM, and its channel activity is correlated with Notch1 activation. Inhibition of TRPM7 downregulates Notch1 signaling, while upregulation of TRPM7 upregulates Notch1 signaling. 3) GSC markers, CD133 and ALDH1, are correlated with TRPM7 in GBM. 4) Targeting TRPM7 suppresses the growth and proliferation of glioma cells through G1/S arrests and apoptosis of glioma cells. 5) Targeting Notch1 suppresses the TRPM7-induced growth and proliferation of glioma cells, as well as the expression of GSC markers CD133 and ALDH1. In summary, TRPM7 is responsible for sustained Notch signaling activation, enhanced expression of GSC markers, and regulation of glioma stemness, which contribute to malignant glioma cell growth and invasion. Notch1 and ligand DII4 are key components that contribute GSC stemness.

scholarly journals TRPM7 Induces Tumorigenesis and Stemness Through Notch Activation in Glioma

2020 ◽  
Vol 11 ◽  
Author(s):  
Jingwei Wan ◽  
Alyssa Aihui Guo ◽  
Pendelton King ◽  
Shanchun Guo ◽  
Talib Saafir ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Notch Signaling ◽  
Glioma Cell ◽  
Kinase Domain ◽  
Normal Brain ◽  
Diffuse Astrocytoma ◽  
Notch1 Signaling ◽  
Aldh1 Expression ◽  
Signaling Activity

We have reported that transient receptor potential melastatin-related 7 (TRPM7) regulates glioma stem cells (GSC) growth and proliferation through Notch, STAT3-ALDH1, and CD133 signaling pathways. In this study, we determined the major contributor(s) to TRPM7 mediated glioma stemness by further deciphering each individual Notch signaling. We first determined whether TRPM7 is an oncotarget in glioblastoma multiforme (GBM) using the Oncomine database. Next, we determined whether TRPM7 silencing by siRNA TRPM7 (siTRPM7) induces cell growth arrest or apoptosis to reduce glioma cell proliferation using cell cycle analysis and annexin V staining assay. We then examined the correlations between the expression of TRPM7 and Notch signaling activity as well as the expression of GSC markers CD133 and ALDH1 in GBM by downregulating TRPM7 through siTRPM7 or upregulating TRPM7 through overexpression of human TRPM7 (M7-wt). To distinguish the different function of channel and kinase domain of TRPM7, we further determined how the α-kinase-dead mutants of TRPM7 (α-kinase domain deleted/M7-DK and K1648R point mutation/M7-KR) affect Notch activities and CD133 and ALDH1 expression. Lastly, we determined the changes in TRPM7-mediated regulation of glioma cell growth/proliferation, cell cycle, and apoptosis by targeting Notch1. The Oncomine data revealed a significant increase in TRPM7 mRNA expression in anaplastic astrocytoma, diffuse astrocytoma, and GBM patients compared to that in normal brain tissues. TRPM7 silencing reduced glioma cell growth by inhibiting cell entry into S and G2/M phases and promoting cell apoptosis. TRPM7 expression in GBM cells was found to be positively correlated with Notch1 signaling activity and CD133 and ALDH1 expression; briefly, downregulation of TRPM7 by siTRPM7 decreased Notch1 signaling whereas upregulation of TRPM7 increased Notch1 signaling. Interestingly, kinase-inactive mutants (M7-DK and M7-KR) resulted in reduced activation of Notch1 signaling and decreased expression of CD133 and ALDH1 compared to that of wtTRPM7. Finally, targeting Notch1 effectively suppressed TRPM7-induced growth and proliferation of glioma cells through cell G1/S arrest and apoptotic induction. TRPM7 is responsible for sustained Notch1 signaling activation, enhanced expression of GSC markers CD133 and ALDH1, and regulation of glioma stemness, which contributes to malignant glioma cell growth and invasion.

scholarly journals CircRNA Circ-ITCH Inhibits the Proliferation and Invasion of Glioma Cells Through Targeting the miR-106a-5p/SASH1 Axis

2021 ◽  
Vol 30 ◽  
pp. 096368972098378
Author(s):  
Wei Chen ◽  
Ming Wu ◽  
Si-Tong Cui ◽  
Yue Zheng ◽  
Zhen Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Polymerase Chain Reaction Analysis ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Glioma Cell Proliferation ◽  
Proliferation And Invasion

Circ-ITCH, a novel circRNA, was generated from several exons of itchy E3 ubiquitin protein ligase (ITCH). Recently, circ-ITCH has been demonstrated to be involved in cancer development. However, there have been few investigations on the specific role of circ-ITCH in glioma. In this study, we performed quantitative real-time polymerase chain reaction analysis and identified that circ-ITCH was significantly downregulated in glioma tissues and cell lines. The function assays showed that upregulation of circ-ITCH inhibited glioma cell proliferation and invasion in vitro as well as reduced cell growth in vivo. Moreover, miR-106a-5p was found serving as a target of circ-ITCH and miR-106a-5p mimics could reverse the inhibitory effect of circ-ITCH on glioma cell proliferation and invasion. We also revealed that circ-ITCH increased SASH1 expression by sponging miR-106a-5p in glioma cells. In addition, SASH1 downregulation could abrogate the suppressive effect of circ-ITCH on glioma progression. Taken together, our results suggested that circ-ITCH could suppress glioma cell proliferation and invasion via regulating the miR-106a-5p/SASH1 axis, elucidating a novel molecular target for glioma treatment.

scholarly journals Role of Jagged1-mediated Notch Signaling Activation in the Differentiation and Stratification of the Human Limbal Epithelium

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1945
Author(s):  
Sheyla González ◽  
Maximilian Halabi ◽  
David Ju ◽  
Matthew Tsai ◽  
Sophie X. Deng
Keyword(s):  
Notch Signaling ◽  
Progenitor Cell ◽  
Basal Layer ◽  
Notch Signaling Pathway ◽  
Basal Cells ◽  
Proliferation Markers ◽  
Limbal Epithelium ◽  
Asymmetric Divisions ◽  
Signaling Activation

The Notch signaling pathway plays a key role in proliferation and differentiation. We investigated the effect of Jagged 1 (Jag1)-mediated Notch signaling activation in the human limbal stem/progenitor cell (LSC) population and the stratification of the limbal epithelium in vitro. After Notch signaling activation, there was a reduction in the amount of the stem/progenitor cell population, epithelial stratification, and expression of proliferation markers. There was also an increase of the corneal epithelial differentiation. In the presence of Jag1, asymmetric divisions were decreased, and the expression pattern of the polarity protein Par3, normally present at the apical-lateral membrane of basal cells, was dispersed in the cells. We propose a mechanism in which Notch activation by Jag1 decreases p63 expression at the basal layer, which in turn reduces stratification by decreasing the number of asymmetric divisions and increases differentiation.

Inhibitory Effect of MicroRNA-376b-Overexpressing Bone Marrow Mesenchymal Stem Cells (BMSCs) on Malignant Characteristics of Glioma Cells Through Targeting Forkhead Box Protein P2 (FOXP2)

2022 ◽  
Vol 12 (5) ◽  
pp. 971-977
Author(s):  
Ruoyu Zhu ◽  
Zhonglin Wang
Keyword(s):  
Glioma Cell ◽  
Potential Role ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
Transwell Assay ◽  
Cell Behaviors ◽  
Forkhead Box ◽  
Marrow Mesenchymal Stem Cells ◽  
The Impact

This study investigated the impact of microRNA (miR)-376b derived from BMSCs on glioma progression. BMSCs were transfected with miR-376b mimic, miR-376b inhibitor or NC and then cocultured with glioma cells followed by measuring cell behaviors by MTT assay, Transwell assay and flow cytometry, FOXP2 and miR-376b expression by Western blot and RT-qPCR. After confirming the inhibitory and mimicking activity of transfection, we found that overexpression of miR-376b in BMSCs decreased glioma cell invasion, migration and proliferation but promoted cell apoptosis within 24 h and 48 h after transfection along with reduced number of cells in S-phase. Mechanically, miR-376b targeted miR-376b and up-regulation of miR-376b caused down-regulation of FOXP2 (p < 0.05). Overexpression of miR-376b in BMSCs decelerated glioma cell cycle and inhibitedmalignant behaviors of glioma cells by targeting FOXP2 expression. These evidence unveils the potential role of FOXP2 as a biomarker for the treatment of gliomas.

Oroxylin A induces autophagy in human malignant glioma cells via the mTOR-STAT3-Notch signaling pathway

2014 ◽  
Vol 54 (11) ◽  
pp. 1363-1375 ◽  
Author(s):  
Meijuan Zou ◽  
Chen Hu ◽  
Qidong You ◽  
Aixia Zhang ◽  
Xuerong Wang ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Glioma Cells ◽  
Notch Signaling Pathway ◽  
Oroxylin A ◽  
Human Malignant Glioma ◽  
Malignant Glioma Cells

scholarly journals CBMT-18. THE ROLE OF BIOMARKER CANDIDATE GELSOLIN AND ITS MICRORNAS IN GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi36-vi37
Author(s):  
Mitsutoshi Nakada ◽  
Jiakang Zhang ◽  
Taskuya Furuta ◽  
Shabierjiang Jiapaer ◽  
Sho Tamai ◽  
...  
Keyword(s):  
Cell Lines ◽  
Glioma Cell ◽  
Glycogen Synthase ◽  
Inverse Correlation ◽  
Progression Free Survival ◽  
Expression Level ◽  
Normal Brain ◽  
Kaplan Meier ◽  
Glioma Cell Lines ◽  
Proliferation And Invasion

Abstract BACKGROUND Among potential glioblastoma (GBM) blood biomarkers that we identified recently, we focused on gelsolin (GSN), a key regulator of actin filament disassembly. GSN was significantly lower in the blood of patients with GBM than in that of healthy controls. In this study, we analyzed the function of GSN and identified microRNAs (miRs) involved in GSN expression in GBM. METHODS QRT-PCR and western blot were introduced to evaluate the expression level of GSN in normal brain and GBM tissue. The localization of GSN was examined by immunohistochemistry and immunocytochemistry using human samples. The association between the expression level of GSN and progression free survival (PFS) /overall survival (OS) in GBM was assessed by Kaplan-Meier analysis. The function of GSN and its signal transduction in glioma cell lines were analyzed using small interfering RNA (siRNA) knockdown of GSN. Additionally, miRs controlling GSN expression were retrieved from databases of miRs, and miRs related to GSN expression were identified in GBM tissues. RESULTS The expression level of GSN was significantly lower in GBM tissues compared to normal brains. Normal astrocytes mainly expressed GSN. High expressor of GSN showed longer PFS and OS than low expressor. Proliferation and invasion in glioma cell lines were significantly promoted by siRNA for GSN accompanied with the activation of glycogen synthase kinase 3β. In GBM tissues, the expression levels of GSN and miR-654-5p, 450b-5p showed an inverse correlation. The inhibitor for miR-654-5p and miR-450b-5p accelerated GSN expression resulting reduction of proliferation. CONCLUSION GSN plays a role as suppressor of proliferation and invasion in GBM. miR-654-5p and miR-450b-5p which control GSN expression can be targets against GBM.

scholarly journals miR-6869-5p Inhibits Glioma Cell Proliferation and Invasion via Targeting PGK1

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Fakai Wang ◽  
Huanjun Zhang ◽  
Bing Liu ◽  
Wei Liu ◽  
Zengchao Zhang
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Negative Association ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Glioma Cell Proliferation ◽  
Precise Role ◽  
Proliferation And Invasion

Accumulating studies have suggested the dysregulated microRNAs (miRNAs) play important roles in brain tumors, including glioma. miR-6869-5p has been documented to be aberrantly expressed in diverse cancers. However, the precise role of miR-6869-5p in glioma remains poorly understood. This study is aimed at evaluating its modifying effects on glioma. Significantly decreased expression of miR-6869-5p was found in glioma tissues and cells. Negative association was documented between miR-6869-5p and PGK1 in glioma cells, and PGK1 was demonstrated to be a targeted gene of this miRNA by luciferase reporter assay. miR-6869-5p regulated glioma cell proliferation and invasion via targeting PGK1. In addition, the survival analysis had suggested that low miR-6869-5p expression predicted poor prognosis of glioma patients. This study has suggested that miR-6869-5p is a useful tumor suppressor and prognostic marker in glioma.

scholarly journals Knockdown of linc-OIP5 inhibits proliferation and migration of glioma cells through down-regulation of YAP-NOTCH signaling pathway

Gene ◽  
2017 ◽  
Vol 610 ◽  
pp. 24-31 ◽  
Author(s):  
Guo-wen Hu ◽  
Lei Wu ◽  
Wei Kuang ◽  
Yong Chen ◽  
Xin-gen Zhu ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathway ◽  
Glioma Cells ◽  
Notch Signaling Pathway ◽  
Down Regulation ◽  
And Migration ◽  
Proliferation And Migration
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